EXPERT REACTION: New international guidelines relax '14 day rule' that limits research on human embryos

The current revision of ISSCR Guidelines for Stem Cell Research and Clinical Translation was necessitated by the recent emergence of new knowledge involving human embryos and embryo manipulation,  including inter-species embryoid formation for research and development.

However, the other major sections of ISSCR guidelines remain unchanged.

These guidelines are very important for the scientific community, the public and particularly the regulatory authorities to continue to develop a framework for facilitating therapeutic development using stem cells and products in areas of unmet medical need in a harmonised manner.

However, these current revisions have failed to address some critical areas of significant importance in regenerative medicine where promising developments have occurred, such as off the shelf clinical development using either stem cells or stem cells-derived product like extracellular vesicles (EV). The regulatory authorities are struggling to cope with requests for these kinds of clinical trials for which there are no framework/guidelines.

These releases from the International Society for Stem Cell Research (ISSCR) reflect the continuing evolution of what scientists are capable of, and how far the boundary should be pushed back to allow a better understanding of human development.  A good example of this relates to the 14 day rule beyond which it is illegal to maintain a human embryo in the laboratory.  It is now technically feasible to maintain a monkey embryo up to 20 days, and the question therefore being asked is whether the same should be allowed with a human embryo.  A knowledge of how certain disorders begin might better be understood if society was to allow this.  The ISSCR is posing the question rather than saying this should be allowed.  Each culture and society will make its own decision. 

The ISSCR call for the need for clear, comprehensive, and consistent regulations governing the marketing and administration of stem cell-based medical therapies is a timely one. Australia currently has few specific mechanisms for assessing premature or inappropriate usage of such interventions.

Registries could be a good means of tracking and sharing data, particularly where randomised clinical trials have not been done. But, ideally, Australia should go beyond such a database to more adequately involving various publics in deliberations about uses of stem cells, which could be accomplished through a more extensive commons approach. A commons could allow collaborative engagement not only with researchers but also with clinicians, regulators, and interested members of the public.

Such a mechanism also could support what perhaps is likely to be the most controversial recommendation from the ISSCR, namely that embryos should be able to be studied beyond 14 days, subject to an individual review of each proposed project, including assessment of “broad public support” and ensurance of use of only a minimal number of embryos.

Again, Australia is well-placed to do such reviews through its long-established and highly respected NHMRC embryo research licensing committee. The ISSCR call for “public conversations” is extremely important, but best practices should be used to foster these including robust empirical methods for using such conversations to shape regulatory or licensing decisions.

Australia does not currently have mechanisms for engaging the public or gauging support for such proposals in an efficient or accurate manner, including considerations of social justice, research prioritisation, or appropriate use of resources.

If the ISSCR guidelines are to be followed, we will need more systematic engagement of diverse publics about their values in relation to stem cell research, and particular types of studies of embryos beyond 14 days. Australia could become a world leader not only in this scientific field but in responsible, transparent, and publicly engaged stem cell research and its applications, if such processes could be put in place.

I was honoured to serve on the global Taskforce that developed these important guidelines. The new guidelines provide a series of detailed and practical recommendations in response to recent scientific and clinical developments.

Specifically, they address the ethical and policy issues raised by the use of human embryos in research; creation of human embryo models using stem cells; use of chimeric animals and embryos in research; clinical translation of stem cell-based therapies, and applications of technologies such as mitochondrial donation and genome editing.

They provide an invaluable reference point for researchers, doctors, industry, funding agency, policy makers, and the public. While national regulations and existing ethical frameworks will need to be taken into consideration, these regularly revised global guidelines provide a basis to drive important discussions around stem cell research at a domestic level.

The new guidelines recognise that some areas of stem cell research require independent ‘specialised’ scientific and ethical review– that includes community members and people with expertise in the relevant science, ethics and law – beyond that usually required and conducted at an institutional level.

The new Guidelines clearly map what type of stem cell research requires a higher level of review, what practices are exempt, and what forms of research continue to be explicitly prohibited due to lack of compelling scientific justification and ethical concerns.

Notably, prohibited activities continue to include a ban on attempts to achieve a pregnancy in a woman using a cloned embryo, model embryos made from human stem cells, or an animal-human embryo.

Research involving the use of human stem cells to make 3D laboratory models that mimic early human embryos, such as the recently reported blastoid research, is an example of permissible research only following rigorous independent specialised review.

The Guidelines will be reviewed again in five years.

As incoming President of the ISSCR, I am incredibly proud of the proactive role that our Society has, and continues to play, in guiding appropriate scientific behaviour and regulatory frameworks in countries across the globe.
 
New scientific approaches are continuing emerge in all areas, but notably around stem cell science. Some of these emerging technologies present ethical challenges, even when the benefit to human health may be the long term objective. This is particularly so in research modelling the human embryo and generating human-animal chimeric tissues. The fact that these guidelines have been developed by the research community itself indicates a deep sense of responsibility and integrity and an active desire to ensure that the science is in step with the community.

As we find that we can generate almost any human tissue from a stem cell, we are also beginning to model the earliest stages of human life. Indeed, researchers here in Australia have shown that this is possible and may hold the key to understanding early challenges to life (this was Jose Polo at Monash Unveirsity). While these are only models, it remains important to have oversight and a framework around appropriate behaviour.
 
With advances in the development of stem cell-based therapies, the creation of tissue combining human and animal cells is needed to prove the value of such treatments before moving to man. This also presents ethical challenges that must be considered.
 
With advances in gene editing, there is the prospect of delivering genetically modified cells. While this brings great promise of new treatments, it is also important to have such research monitored and approved.
 
In all instances, the Guidelines outline where a technology has potential to do good but must have regulatory oversight.